Transplantation of retinal pigment epithelial (RPE) cells and iris pigment epithelial (IPE) cells, as a means to rescue or restore diseased photoreceptors in a sub-retinal space, is a leading experimental therapy for treating age-related macular degeneration (AMD), the most common form of blindness for persons over age 65 in Western nations. A sub-retinal space is a space adjacent to or underneath the retina, where the eye's photoreceptors are located.
The pathogenesis of AMD involves death of RPE cells at the posterior of the eye, underneath the retina in the sub-retinal space. The RPE membrane (Bruch's membrane) is also damaged in AMD because of new blood vessel growth and other factors related to normal aging. Death of the photoreceptor cells, and eventual blindness, follows death of the RPE cells.
One current theory suggests that replacement of dying RPE cells in the sub-retinal space may rescue or restore the function(s) of the photoreceptor cells. First attempts at RPE cell transplantation involved injecting a suspension of RPE cells into a patient's sub-retinal space. This approach was supplanted by transplant of intact sheets of RPE cells. Each of these techniques was plagued with problems arising from disorientation of the transplanted cells and from destruction of the Bruch's membrane in the AMD process.
One form of treatment of AMD is growth of RPE cells and/or IPE cells on a suitable support material and transplantation of cells and support material into the sub-retinal space of the eye. The RPE and IPE cells have been shown to survive after injection into the sub-retinal space as single cell suspensions, as patches of cells, and as sheets of confluent cells. However, the inability of these transplanted cells to spontaneously form an organized monolayer and perform phenotypic functions of native RPE cells may be a cause of ineffectiveness of this type of treatment. It has been suggested that transplanted RPE cells perform poorly in the pathological sub-retinal space because such cells attach poorly to a damaged Bruch's membrane of eyes affected by AMD. The Bruch's membrane can become damaged because of growth of new vessels. Transplantation of cell suspensions, or even of patches or confluent sheets of such cells, may be ineffective for AMD treatment.
One possible approach is to grow RPE and/or IPE on a suitable support material and to transplant both the cells and the support material into the sub-retinal space. Growth properties and related characteristics of pigment epithelial cells are greatly influenced by the surface properties of the substrate on which the cells are grown. Choroidal neovascularization, which is a characteristic of the wet/exudative form of AMD, may also be prevented by the support material by mechanical blockage. Additionally, use of support material will allow for transplantation of large sheets and monolayers of RPE and IPE. The surface of the support material may be modified to affect or control the growth properties of the transplanted RPE cells and/or IPE cells. The growth properties and characteristics of pigment epithelial cells are greatly influenced by the surface properties of the growth substrate. Several groups have studies different materials, such as anterior lens capsule and Descemet's membrane, for transplantation of RPE cells and IPE cells into the sub-retinal space. These attempts have been unsuccessful because of the handling properties of the support materials used by these experimenters. Although cells have been grown on lens capsule, it is difficult to implant lens capsule into the sub-retinal space, due to its tendency to curl on itself, especially in an aqueous environment. It is an even greater challenge to maintain lens capsule material flat when the material is implanted into the sub-retinal space. Additionally, use of a 10–15 μm thick lens capsule structure to replace a 2-μm thick layer of Bruch's membrane may pose some diffusion problems for the transplanted RPE and IPE cells and for the remaining retina. It is not yet known how porous lens capsule material and Descemet's membrane material are and whether these materials will allow for proper diffusion of nutrients, waste, oxygen and carbon dioxide.
What is needed is a support material that (1) is biocompatible, (2) will serve as a surface for growing selected cells or sheets of cells, (3) is moderately strong, (4) has a controllable range of porosity, and (5) will not spontaneously roll up or form creases.